Progesterone (P) receptors appear in granulosa cells of preovulatory follicles after the midcycle gonadotropin surge, suggesting important local actions of P during ovulation in primates. Steroid reduction and replacement during the gonadotropin surge in macaques was used to evaluate the role of P in the ovulatory process. Rhesus monkeys received gonadotropins to induce development of multiple preovulatory follicles, followed by human chorionic gonadotropin (hCG) administration (day 0) to promote oocyte (nuclear) maturation, ovulation, and follicular luteinization. On days 0-2, animals received 1) no further treatment (controls; n=4); 2) the 3 -hydroxysteroid dehydrogenase inhibitor, trilostane (TRL; n=3); 3) TRL plus the P agonist, R5020 (n=3); or 4) TRL plus the nonmetabolizable androgen, dihydrotestosterone-propionate (DHT; n=3). On day 3, ovulation was confirmed by counting ovulation sites and collecting oviductal oocytes. The meiotic status of oviductal and remaining follicular oocytes was evaluated. Peak serum estradiol levels, the total number of large (2-6 mm diameter) follicles, and baseline serum P levels at the time of hCG administration were similar in all animals. Multiple ovulation sites and oviductal oocytes were observed in controls, but TRL abolished ovulation. Progestin, but not androgen, replacement restored ovulation to control levels. Whereas the percentage of mature (metaphase II) oocytes recovered did not differ among groups (s89% of oocytes), the fertilization rate of oocytes from TRL-treated animals was less than controls (16 vs 82%). Serum P levels remained at baseline during TRL, and throughout the luteal phase compared to controls (s5 ng/ml vs 49 ng/ml days 4-6 post-hCG, respectively). However, R5020 and DHT replacement with TRL restored P levels to that of controls by day 6 and day 8 of the luteal phase, respectively. Thus, steroid reduction during the gonadotropin surge inhibited ovulation and luteinization, but not reinitiation of oocyte meiotic maturation, in the primate follicle. The data are consistent with a local receptor-mediated role for P in the ovulatory process.